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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
medicine
Drug resistance and viral tropism in HIV-1 subtype C-infected patients in KwaZulu-Natal, South Africa: Implications for future treatment options
Journal of Acquired Immune Deficiency Syndromes, Volume 58, No. 3, Year 2011
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Description
Background: Drug resistance poses a significant challenge for the successful application of highly active antiretroviral therapy (HAART) globally. Furthermore, emergence of HIV-1 isolates that preferentially use CXCR4 as a coreceptor for cell entry, either as a consequence of natural viral evolution or HAART use, may compromise the efficacy of CCR5 antagonists as alternative antiviral therapy. Methods: We sequenced the pol gene of viruses from 45 individuals failing at least 6 months of HAART in Durban, South Africa, to determine the prevalence and patterns of drug-resistance mutations. Coreceptor use profiles of these viruses and those from 45 HAART-naive individuals were analyzed using phenotypic and genotypic approaches. Results: Ninety-five percent of HAART-failing patients had at least one drug-resistant mutation. Thymidine analog mutations (TAMs) were present in 55% of patients with 9% of individuals possessing mutations indicative of the TAM1 pathway, 44% had TAM2, whereas 7% had mutations common to both pathways. Sixty percent of HAART-failing subjects had X4/dual//mixed-tropic viruses compared with 30% of HAART-naïve subjects (P < 0.02). Genetic coreceptor use prediction algorithms correlated with phenotypic results with 60% of samples from HAART-failing subjects predicted to possess CXCR4-using (X4/dual/mixed viruses) versus 15% of HAART-naïve patients. Conclusions: The high proportion of TAMs and X4/dual/mixed HIV-1 viruses among patients failing therapy highlight the need for intensified monitoring of patients taking HAART and the problem of diminished drug options (including CCR5 antagonists) for patients failing therapy in resource-poor settings. © 2011 Lippincott Williams & Wilkins.
Authors & Co-Authors
Singh, Ashika
South Africa, Durban
University of Kwazulu-natal
Sunpath, Henry
South Africa, Durban
Mccord Hospital
Green, Taryn N.
South Africa, Durban
University of Kwazulu-natal
Padayachi, Nagavelli
South Africa, Durban
University of Kwazulu-natal
Hiramen, Keshni
South Africa, Durban
University of Kwazulu-natal
Lie, Yolanda S.
United States, San Francisco
Monogram Biosciences
Anton, Elizabeth D.
United States, San Francisco
Monogram Biosciences
Murphy, Richard A.
Switzerland, Geneva
Medecins Sans Frontieres
Reeves, Jacqueline D.
United States, San Francisco
Monogram Biosciences
Kuritzkes, Daniel R.D.
United States, Boston
Brigham and Women's Hospital
United States, Boston
Harvard Medical School
Ndung'u, Thumbi P.
South Africa, Durban
University of Kwazulu-natal
Statistics
Citations: 25
Authors: 11
Affiliations: 6
Identifiers
Doi:
10.1097/QAI.0b013e318228667f
ISSN:
15254135
Research Areas
Cancer
Genetics And Genomics
Infectious Diseases
Study Design
Cross Sectional Study
Study Locations
South Africa